Midbrain dopamine neurons in Parkinson׳s disease exhibit a dysregulated miRNA and target-gene network

Briggs, Christine; Wang, Yulei; Kong, Benjamin Y.; Woo, Tsung-Ung W.; Iyer, Lakshmanan K.; Sonntag, Kai‐Christian

doi:10.1016/j.brainres.2015.05.021

Cited by 95 publications

(96 citation statements)

References 99 publications

(83 reference statements)

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“…miRNAs impact on α-synuclein expression raises the hypothesis that dysregulated miRNAs in PD patients are responsible for α-synuclein upregulation and/or accumulation. Supporting this idea, several studies have demonstrated that PD patients exhibited dysregulated miRNAs in brain (Kim et al, 2007; Cardo et al, 2013; Miñones-Moyano et al, 2013; Briggs et al, 2015; Hoss et al, 2016), blood (Margis et al, 2011; Martins et al, 2011; Khoo et al, 2012; Botta-Orfila et al, 2014; Burgos et al, 2014), cerebrospinal fluid (CSF; Burgos et al, 2014; Gui et al, 2015; Hossein-Nezhad et al, 2016) and medulla (Liao et al, 2013). …”

Section: Discussionmentioning

confidence: 93%

Role of microRNAs in the Regulation of α-Synuclein Expression: A Systematic Review

Recasens

Perier

Sue

2016

Front. Mol. Neurosci.

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Growing evidence suggests that increased levels of α-synuclein might contribute to the pathogenesis of Parkinson’s disease (PD) and therefore, it is crucial to understand the mechanisms underlying α-synuclein expression. Recently, microRNAs (miRNAs) have emerged as key regulators of gene expression involved in several diseases such as PD and other neurodegenerative disorders. A systematic literature search was performed here to identify microRNAs that directly or indirectly impact in α-synuclein expression/accumulation and describe its mechanism of action. A total of 27 studies were incorporated in the review article showing evidences that six microRNAs directly bind and regulate α-synuclein expression while several miRNAs impact on α-synuclein expression indirectly by targeting other genes. In turn, α-synuclein overexpression also impacts miRNAs expression, indicating the complex network between miRNAs and α-synuclein. From the current knowledge on the central role of α-synuclein in PD pathogenesis/progression, miRNAs are likely to play a crucial role at different stages of PD and might potentially be considered as new PD therapeutic approaches.

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Section: Discussionmentioning

confidence: 93%

Role of microRNAs in the Regulation of α-Synuclein Expression: A Systematic Review

Recasens

Perier

Sue

2016

Front. Mol. Neurosci.

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“…MicroRNA-181a has been shown to be dysregulated in PD patients, suggesting that it may contribute to the underlying pathology, while it has also been proposed as a potential disease biomarker [13,14].…”

Section: Discussionmentioning

confidence: 99%

“…We first sought to gain insight into the biological processes that may be altered by elevated miR-181a expression in the mDA neurons in PD [13]. To do this, we used miRecords to create a list of putative miR-181a mRNA targets predicted by at least four prediction programs [20].…”

Section: In Silico Analysis Implicates Mir-181a As a Regulator Of Bmpmentioning

confidence: 99%

“…miRNA are widely expressed in the brain, where they control the development, survival, function and plasticity of neurons [9][10][11][12]. miRNA dysregulation has been implicated in the pathophysiology of a range of neurological disorders, including PD [12,13]. One miRNA, miR-181a, has been shown to be upregulated in mDA neurons in PD [13].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of miR-181a promotes midbrain neuronal growth through a Smad1/5-dependent mechanism: implications for Parkinson’s disease

2018

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Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Current PD treatments are symptomatic, wear off over time, and do not protect against DA neuronal loss. Finding a way to re-grow mDA neurons is a promising disease-modifying therapeutic strategy for PD. However, reliable biomarkers are required to allow such growth-promoting approaches to be applied early in the disease progression. MicroRNA-181a has been shown to be dysregulated in PD patients, and has been identified as a potential biomarker for PD. Despite studies demonstrating the enrichment of miR-181a in the brain, but more specifically in neurites of postmitotic neurons, the role of miR-181a in mDA neurons remained unknown. Herein, we used cell culture models of human mDA neurons to investigate a potential role for miR-181a in mDA neurons. We used a bioninformatics analysis to identify that miR-181a targets components of the bone morphogenetic protein (BMP) signalling pathway, including the transcription factors Smad1 and Smad5, which we find are expressed by rat mDA neurons and are required for BMP-induced neurite growth. We also found that inhibition of neuronal miR-181a, resulted in increased Smad signalling, and induced neurite growth in SH-SY5Y cells. Finally, using embryonic rat cultures, we demonstrated that miR-181a inhibition induces ventral midbrain and cortical neuronal growth. These data describe a new role for miR-181a in mDA neurons, and provide proof-of principle that miR-181a dysresgulation in PD may alter the activation state on signalling pathways important for neuronal growth. KeywordsMicroRNA-181a, midbrain neurons, neurite growth, bone morphogenetic protein, Smad signalling.

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“…One conserved ncRNA pathway was identified through miRNA expression profiles of midbrain dopamine neurons (mDNs) in PD patients (Kim et al, 2007; Briggs et al, 2015). One of the dysregulated miRNAs, miR-133b, controls mDN differentiation through a feedback loop with Pitx3 (Kim et al, 2007).…”

Section: Mirna-mediated Regulation Of Dopamine Signaling In Neurologimentioning

confidence: 99%

Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

Carrick

Burks

Cairns

et al. 2016

Front. Mol. Biosci.

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Dopaminergic neurotransmission mediates a majority of the vital central nervous system functions. Disruption of these synaptic events provokes a multitude of neurological pathologies, including Parkinson's, schizophrenia, depression, and addiction. Growing evidence supports a key role for noncoding RNA (ncRNA) regulation in the synapse. This review will discuss the role of both short and long ncRNAs in dopamine signaling, including bioinformatic examination of the pathways they target. Specifically, we focus on the contribution of ncRNAs to dopaminergic dysfunction in neurodegenerative as well as psychiatric disease.

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Midbrain dopamine neurons in Parkinson׳s disease exhibit a dysregulated miRNA and target-gene network

Cited by 95 publications

References 99 publications

Role of microRNAs in the Regulation of α-Synuclein Expression: A Systematic Review

Role of microRNAs in the Regulation of α-Synuclein Expression: A Systematic Review

Inhibition of miR-181a promotes midbrain neuronal growth through a Smad1/5-dependent mechanism: implications for Parkinson’s disease

Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

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